Analysis of cytomegalovirus-specific T-cell responses in patients with hypertension: comparison of assay methods and antigens

Jong-Chan Youn,Eui-Cheol Shin,Su-Hyung Park,Jun Yong Kim,Min Kyung Jung,Hee Tae Yu,Sungha Park,In-Cheol Kim,Kyu-Hyung Ryu,Suk-Won Choi,Sun Ki Lee,Seongwoo Han

doi:10.1186/s40885-018-0090-8

Abstract

BackgroundRecent studies suggest an association between cytomegalovirus (CMV) infection and hypertension. In the present study, we used a variety of antigens and different assay methods to investigate the relationship between CMV-specific T-cell responses and arterial stiffness in patients with hypertension.MethodsTo evaluate arterial stiffness, pulse wave velocity (PWV) was measured in 207 hypertensive patients (average age, 63 ± 8 years). To measure CMV pp65 and IE-1-specific T-cell responses, we performed intracellular cytokine staining (ICS) and enzyme-linked immunospot (ELISPOT) assays. We also analyzed CMV-specific T-cell responses against 10 different CMV antigens using ELISPOT assays.ResultsIn patients with hypertension, senescent CD8+ T-cell frequencies were significantly correlated with arterial stiffness. Moreover, arterial stiffness was independently associated with CMV pp65-specific CD8+ T-cell responses as measured by ICS. CMV-specific CD8+ T-cell responses measured by ICS and ELISPOT assays showed good agreement and significant correlation with each other. ELISPOT analyses against 10 different CMV antigens revealed a consistent response pattern irrespective of age, gender, and diabetesConclusionsCMV pp65-specific CD8+ T-cell responses were independently correlated with arterial stiffness in patients with hypertension. Additionally, the results of ICS and ELISPOT assays showed a significant correlation and good agreement with each other. These findings are important for guiding choices regarding the broad clinical application of CMV-specific T-cell response assays in this patient population.

Highlights

Recent studies suggest an association between cytomegalovirus (CMV) infection and hypertension
Enzyme-linked immunospot (ELISPOT) assays for 10 different CMV antigens revealed a consistent response pattern irrespective of age, gender, and diabetes we investigated CMV-specific IFN-γ-producing CD8+ T-cell responses by performing ELISPOT assays using 10 different CMV antigens
Our present results showed that arterial stiffness in patients with hypertension was correlated with the frequency of senescent CD8+ T cells, and independently associated with the CMV pp65-specific CD8+ T-cell response measured by intracellular cytokine staining (ICS)

Summary

Introduction

Recent studies suggest an association between cytomegalovirus (CMV) infection and hypertension. We used a variety of antigens and different assay methods to investigate the relationship between CMV-specific T-cell responses and arterial stiffness in patients with hypertension. Recent evidence suggests that infection with cytomegalovirus (CMV) [1,2,3] and T cell-driven inflammation [4,5,6] play pathogenic roles in the development of hypertension. We recently demonstrated that CMV-specific T-cell responses are independently associated with arterial stiffness, suggesting related pathophysiological mechanisms [17]. We used a variety of antigens and different assay methods to examine examined the relationship between CMV-specific T-cell responses and arterial stiffness in patients with hypertension

Methods

Results

Discussion

Conclusion